Tumor gene screening to assign drug combinations in advanced solid tumors

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for people with solid tumors that have spread nearby or elsewhere in the body. The cancer must have worsened on standard treatment, or have no standard treatment that prolongs survival.

Age

Adults 18 years and older, and also people under 18 who have stored tumor tissue available.

Sex

All sexes can join.

Disease stage

Locally advanced or advanced solid tumors needing treatment, with disease that can be measured.

Earlier treatment

The cancer must have progressed on at least one line of standard systemic therapy, or have no standard treatment shown to prolong overall survival.

Biomarker or test result

Tumor gene sequencing results from an NCI credentialed Designated Laboratory must be available.

Main reasons for not taking part

• No measurable disease
• ECOG performance status above 2, or Lansky or Karnofsky status below 50%
• No sequencing results from an NCI credentialed Designated Laboratory
• Not seen by the enrolling provider as potentially able to join a ComboMATCH Treatment Trial
• No biopsiable tumor and no archival tumor tissue available

The registry criteria, word for word

What the trial wants to find out

This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.

The 20 groups in the trial

• EAY191-A2 (Cohort 1, Arm A)Treatment being tested

  Cohort 1, Arm A: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

  Treatment: Alpelisib, Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Magnetic Resonance Imaging, Olaparib, and Positron Emission Tomography

• EAY191-A2 (Cohort 2, Arm B)Treatment being tested

  Cohort 2, Arm B: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

  Treatment: Alpelisib, Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Magnetic Resonance Imaging, Olaparib, and Positron Emission Tomography

• EAY191-A2 (Cohort 2, Arm C)Treatment being tested

  Cohort 2, Arm C: Patients receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients experiencing disease progression have the option to migrate to Cohort 3, Arm D. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

  Treatment: Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Magnetic Resonance Imaging, Olaparib, and Positron Emission Tomography

• EAY191-A2 (Cohort 3, Arm D)Treatment being tested

  Cohort 3, Arm D: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

  Treatment: Alpelisib, Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Olaparib, and Positron Emission Tomography

• EAY191-A3 Combo Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)Treatment being tested

  Patients receive palbociclib PO and binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.

  Treatment: Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Magnetic Resonance Imaging, and Palbociclib

• EAY191-A3 Monotherapy Cohort 1 (binimetinib)Treatment being tested

  Patients receive binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.

  Treatment: Binimetinib, Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, and Magnetic Resonance Imaging

• EAY191-A6 Arm I (RAS/RAF/MEK/ERK mutations)Treatment being tested

  Patients receive leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or a FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated.

  Treatment: Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Echocardiography Test, Fluorouracil, Leucovorin, Magnetic Resonance Imaging, Multigated Acquisition Scan, Oxaliplatin, and Positron Emission Tomography

• EAY191-A6 Arm II (RAS/RAF/MEK/ERK mutations)Treatment being tested

  Patients receive binimetinib PO, leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated

  Treatment: Binimetinib, Biospecimen Collection, Bone Scan, Computed Tomography, Echocardiography Test, Fluorouracil, Leucovorin, Magnetic Resonance Imaging, Multigated Acquisition Scan, Oxaliplatin, and Positron Emission Tomography

• EAY191-E4 (taxane therapy)Treatment being tested

  Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI during screening or cycle 1 day 1, every 2 cycles for 1 year, every 3 cycles for patients on study for more than 1 year, and every 4 cycles for patients on study for more than 3 years and may also undergo CT or MRI during follow-up every 3 months for 2 years and then every 6 months for 1 year if clinically indicated. Patients also undergo collection of blood samples at baseline, cycle 2 day 1, and optionally at progression as well as tumor biopsy at baseline and optionally at progression.

  Treatment: Biopsy Procedure, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Nilotinib Hydrochloride Monohydrate, and Paclitaxel

• EAY191-E5 Cohort I Arm A (sotorasib, panitumumab)Treatment being tested

  Patients receive sotorasib PO QD on days 1-28 and panitumumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.

  Treatment: Biopsy Procedure, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Panitumumab, and Sotorasib

• EAY191-E5 Cohort I Arm B (sotorasib)Existing treatment, for comparison

  Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.

  Treatment: Biopsy Procedure, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, and Sotorasib

• EAY191-E5 Cohort II (sotorasib)Treatment being tested

  Patients receive combination therapy as in EAY191-E5 Arm A.

  Treatment: Biopsy Procedure, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Panitumumab, and Sotorasib

• EAY191-N2 Cohort I (Arm I) (NF1 mutations)Treatment being tested

  Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.

  Treatment: Binimetinib, Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Echocardiography Test, Fulvestrant, Magnetic Resonance Imaging, and Multigated Acquisition Scan

• EAY191-N2 Cohort I (Arm II) (NF1 mutations)Treatment being tested

  Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.

  Treatment: Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Echocardiography Test, Fulvestrant, Magnetic Resonance Imaging, and Multigated Acquisition Scan

• EAY191-N2 Cohort II (NF1 mutations)Treatment being tested

  Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.

  Treatment: Binimetinib, Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Echocardiography Test, Fulvestrant, Magnetic Resonance Imaging, and Multigated Acquisition Scan

• EAY191-N4 Arm I (RAS pathway mutations)Treatment being tested

  Patients receive selumetinib PO BID and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.

  Treatment: Biopsy Procedure, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Echocardiography Test, Multigated Acquisition Scan, Mutation Carrier Screening, Olaparib, and Selumetinib Sulfate

• EAY191-N4 Arm II (RAS pathway mutations)Existing treatment, for comparison

  Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.

  Treatment: Biopsy Procedure, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Echocardiography Test, Multigated Acquisition Scan, Mutation Carrier Screening, and Selumetinib Sulfate

• EAY191-N5 Arm I (neratinib maleate)Existing treatment, for comparison

  Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.

  Treatment: Biopsy Procedure, Biospecimen Collection, Computed Tomography, Echocardiography Test, Magnetic Resonance Imaging, Multigated Acquisition Scan, and Neratinib Maleate

• EAY191-N5 Arm II (neratinib maleate,palbociclib)Treatment being tested

  Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.

  Treatment: Biopsy Procedure, Biospecimen Collection, Computed Tomography, Echocardiography Test, Magnetic Resonance Imaging, Multigated Acquisition Scan, Neratinib Maleate, and Palbociclib

• EAY191-S3 (activating AKT mutation)Treatment being tested

  Patients receive paclitaxel IV on days 1, 8, and 15 and ipatasertib PO on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up.

  Treatment: Biopsy Procedure, Biospecimen Collection, Computed Tomography, Ipatasertib, Magnetic Resonance Imaging, and Paclitaxel